A First-in-Human Study of SON-DP in Participants With Relapsed/Refractory Intolerant to Standard of Care Therapies for Advanced/Metastatic Solid Tumors

- In an effort to overcome the major challenges of the conventional cancer

cell-killing therapy for high side effect, drug resistance, cancer recurrence and

tumor heterogenicity, Qurgen Inc. is developing a novel transcription factor (TF)

protein anticancer drug, named SON-DP, to treat the Participants with relapsed and

advanced metastatic solid tumors. Proposed as an effective therapeutic drug product

for a cell-converting cancer therapy, SON-DP is expected to transform cancer cells

in situ into normal tissue cells via a SON-DP induced cancer cell reprogramming and

re-differentiation process as an innovative rationale.

- SON-DP is developed based on the rationale of cancer cell conversion into normal

tissue cells as the primary mechanism of actions of a new cancer therapy, not by

cancer cell-killing, the traditional goals of chemotherapy, radiation therapy,

targeted therapy and immune therapy. Cancer cell conversion is achieved by the

SON-DP induced pluripotent re-programming in situ inside tumor tissue into transient

iPSCs (tiPSCs) that quickly re-differentiate into normal tissue cells induced by the

differentiating resident tissue environment. The in situ generated tiPSCs either

secrete exosomes, providing the embryonic stem cells (ESC)-like microenvironments to

transform the surrounding cancer cells into normal tissue cells for an overall

malignant phenotype reversion (OMPR) (an effect named as a bystander effect), or

display a targeting effect that enables the in situ generated tiPSCs to track down

the distant metastatic cancer cells for OMPR (an effect named as a tropism effect).

The SON-DP-induced cell reprogramming also restored the mutation-caused and

compromised p53 checkpoint in cancer cells to re-establish cell quality control

system that ensures the downstream re-differentiation of the in situ generated

tiPSCs into normal tissue cells. Overall, this SON-DP-induced re-programming and

re-differentiation process is capable of transforming both primary and metastatic

cancer cells into normal tissue cells.

- Preclinical studies demonstrated that treatment of tumors with SON-DP resulted in

eradication of late-stage cancers and long term (over 3 years) survival without

teratoma formation and cancer recurrence in multiple tumor-bearing mouse/rat

(syngeneic) or human xenograft rodent models, providing high treatment efficacy of

this cell-converting cancer therapy. Thus, the cell-converting cancer therapy

rationale represents a new cancer therapeutic strategy. SON-DP was tolerated in

tumor-bearing rodents, as well as in naïve rats, dogs, and monkeys as demonstrated

by GLP-enabled (rats and dogs) and non-GLP (monkey) toxicity study and after

repeated IV administrations at higher doses compared with the planned clinical dose

range. Therefore, the current nonclinical studies, including pharmacodynamics (PD),

pharmacokinetics (PK) and toxicology studies, support the safety and efficacy of

SON-DP TF protein drug product to be used in clinical studies of human participants.

This first-in-human (FIH) clinical study will be conducted in selected types of

relapsed/refractory advanced/metastatic solid tumors as a step in demonstrating the

utility of this anticancer agent.

- In this SON-DP-A001-ST clinical trial, SON-DP is given to the participants with late

stage solid tumors through 90-minutes IV infusion either once a week or twice a week

at first 4 dose levels during the first Phase I dose escalation stage with the

purpose to identify the final schedule (either once a week or twice a week) for the

last 3 higher dose levels and the recommended phase II dose (RP2D) for the second

Phase Ib does expansion stage that will focus on 4 cancer types including breast

cancer, pancreatic cancer, ovarian cancer and colorectal cancer.

- During Phase Ia dose escalation stage, an accelerated 3+3 design will be followed. A

Safety Monitoring Committee (SMC) will be formed to evaluate all the safety,

efficacy, pharmacokinetic and pharmacodynamic data of each dose level cohort to

decide if the SON-DP dose level should be either escalated to the next dose level or

de-escalated to one level below or determination of maximum tolerated dose (MTD) or

RP2D confirmation or others. Phase Ia will enroll the participants with various

types of solid tumors that metastasized and not response to standard treatment.

- During Phase Ib dose expansion stage, SON-DP will be used, at RP2D dose level, to

treat the participants with 4 specific cancer types including breast cancer,

pancreatic cancer, ovary cancer or colorectal cancer. Four groups of cancer cohorts

will be opened with eligible participants who have relapsed/refractory/intolerant to

standard of care therapies of these four advanced/metastatic solid tumors.

Participants will be followed for safety, confirmation of the RP2D, PK, PD, and

anti-tumor activity as measured by standard assessment tools.